Onychomycosis is a common infection of the fingernails and toenails which causes nails to become thickened and discolored. Elewski B E. Onychomycosis: pathogenesis, diagnosis, and management. Clin Microbiol Rev. 1998; 11:415-29. The estimated incidence of onychomycosis is 8-14% but increases with age and may be as high as 50% among those older than 70 years. Gupta A K, Jain H C, Lynde C W, et al. Prevalence and epidemiology of onychomycosis in patients visiting physicians' offices: a multicenter Canadian survey of 15,000 patients. Am Acad Dermatol. 2000; 43(2 Pt 1):244-8; Ghannoum M A, Hajjeh R A, Scher R, et al. A large-scale North American study of fungal isolates from nails: the frequency of onychomycosis, fungal distribution, and antifungal susceptibility patterns. J Am Acad Dermatol. 2000; 43:641-8.
Tavaborole is a broad-spectrum oxaborole antifungal agent. It is a highly specific protein synthesis inhibitor that targets fungal cytoplasmic leucyl-tRNA synthetase (LeuRS), an aminoacyl-tRNA synthetase. Rock F L, Mao W, Yaremchuk A, et al. An antifungal agent inhibits an aminoacyl-tRNA synthetase by trapping tRNA in the editing site. Science. 2007; 316:1759-6 These enzymes play a pivotal role in maintaining and translating the genetic code within fungal DNA. Tavaborole binds to the active editing site and traps tRNA, preventing catalytic turnover and synthesis of leucine-charged tRNAs. In this way, tavaborole inhibits cellular protein synthesis and thus suppresses fungal activity. In an in vitro permeation model using ex vivo human cadaver fingernails, tavaborole exhibited greater penetration into the nail plate and achieved 250-fold greater quantity through the nail compared with ciclopirox. Hui X, Baker S J, Wester R C, et al. In vitro penetration of a novel oxaborole antifungal (AN2690) into the human nail plate. J Pharm Sci. 2007; 96:2622-31.
The impact of diseases of the nail, such as onychomycosis, on an individual are not insignificant. Lubeck et al. Quality of Life Research, Vol. 8, p. 121-129 (1999). Sufferers of fingernail dystrophy may limit activities which require fine touch such as typing or playing a musical instrument, and sufferers of toenail dystrophy may experience pain or discomfort walking, standing, and exercising. Sufferers of onychomycosis have reported issues such as paresthesia, loss of fine touch, pain and problems retrieving small objects, as well as psychosocial effects connected with nail appearance such as embarrassment and social withdrawal. Drake et al., J. Am. Acad. Dermatol. 1998; 38: 702-704.
Surprisingly, it has been discovered that delivery of 5-halogen benzoxaboroles through a mammalian nail can be increased by placing at least one additional layer of material over the mammalian nail before the application of the 5-halogen benzoxaborole to the mammalian nail. The advantages provided by compositions, methods, and kits utilizing this finding, as well as others, are described herein.